6xfu/epirubicin/cyclophosphamide (fec) compared to 3xfec-3xdocetaxel in high-risk node-negative breast cancer patients

Conditions: Breast Cancer

Summary: in low-risk node-negative breast cancer patients adjuvant chemotherapy should be spared. the identification of this subgroup can be based either on clinical and pathological or on tumour-biological criteria. due to their high prognostic impact, the tumour-biological invasion markers upa/pai-1 (urokinase-type plasminogen activator and its inhibitor pai-1) are potential candidates to effectively assess the risk of relapse in node-negative breast cancer. this study is aimed to compare the risk assessment by the traditional clinico-pathological factors and by tumour-biological factors. the second study question refers to the comparison between an adjuvant combination treatment with fe100c\*6 and a sequential treatment with fe100c\*3 and docetaxel\*3.

1. to compare fec\*6 with fec\*3 followed by doc\*3 with regard to: * the primary endpoint of the study: disease-free survival (dfs) * the secondary endpoints: overall survival (os), compliance, and toxicity of chemotherapy in each patient group 2. to compare patients with low risk according to clinico-pathological versus those according to biological risk criteria with regard to: * the proportion of low risk versus high risk patients * dfs * os (secondary endpoint)

Eligibility criteria:
inclusion criteria: * histological proven primary breast cancer * tumour size \>0.5 cm and \<5 cm (pt1b-pt2, pn0, m0) * axillary lymph nodes tumour free (node-negative disease) * adequate surgical procedure: r0-resection and axillary dissection with more than 10 lymph nodes examined or adequate sentinel procedure in a qualified centre * frozen tumour tissue available (for analysis of biological markers and microarrays, centres with biological risk assessment only). the material has to be stored in liquid nitrogen immediately after excision. * paraffin blocks or (at least) pathology slides of primary tumour (stained and unstained) and axillary nodes (stained) available for central review. * her-2/neu determination by immunohistochemistry. patients will be stratified to be her-2/neu-negative or her-2/neu-positive (her-2/neu score 3+, or her-2/neu score 2+ and fish positive). * no distant metastasis * age \>18 years, \<70 years * performance status ecog \<2 (who performance status 0-1) * adequate cardiac function (echocardiographically measured left ventricular ejection fraction (lvef) or shortening fraction (sf) within the normal limits, i.e. ≥55%) * adequate bone function (neutrophil count \>1.5 x109 /l and platelet count \>100 x109 /l) * adequate renal function (serum creatinine \<120 µmol/l or 1.35 mg/dl) and hepatic function (serum bilirubin \<1 x unl, asat or alat (sgot or sgpt) \<2,5 x unl) * before patient registration/randomization, written informed consent must be obtained according to ich/eu gcp, and national/local regulations exclusion criteria: * chemotherapy contraindicated * inflammatory breast cancer, tumour infiltrated axillary lymph nodes including the sentinel node. * other concomitant pathology compromising survival (at entry), or preventing the administration of chemotherapy with either fec or docetaxel * other serious illness or medical condition that may interfere with the understanding and giving of informed consent and the conduct of the study * estimated life-expectancy \<10 years (irrespective of breast cancer diagnosis) * patient not accessible for treatment and follow up * endocrine treatment not according to the latest standard recommendations of the ago kommission "mamma" * pregnancy, lactation (sufficient non-hormonal contraception in fertile women required) * surgery more than six weeks ago at the start of chemotherapy * pre-existing polyneuropathy * previous or concomitant other malignancy (including contralateral breast cancer) except adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix * prior chemotherapy or radiotherapy or endocrine therapy

Keywords: high risk breast cancer low risk breast cancer upa urokinase-type plasminogen activator pai plasminogen activator inhibitor-type